Progestin-regulated uterine proteins are believed to play major roles in pregnancy. Therefore we searched and identified for the first time a "progestagen-associated human endometrial protein" or PEP which is synthesized within the endometrium. It is emphasized that PEP is perhaps the only major human endometrial protein the synthesis of which is dramatically increased during early pregnancy. However both the hormonal control as well as the role of PEP are poorly understood. Based on the results of studies on progestin-dependent uterine proteins in animals undertaken by other investigators and our own experience with PEP we postulate that PEP synthesis is regulated mainly by progesterone and that PEP plays a role(s) in immunosuppression, protease inhibition or steroid binding. To test this hypothesis we propose to undertake a 3-year study with the following specific aims. 1. To study effects of steroid hormones on in vitro synthesis of PEP by proliferative human endometrium. 2. To purify PEP required to study its role, and 3. To determine the role of PEP in immunosuppression, specifically to test a. whether PEP interacts directly with leucocytes to alter their proliferation response to mitogens (or antigens) or to impair their ability to synthesize immunoglobulins or b. whether PEP interacts with placental (fetal) cell membranes (thereby masking the fetal antigens on cell membranes and preventing their recognition by the immune system). PEP will be purified by the conventional protein fractionation techniques. PEP synthesis by endometria and immunoglobulin synthesis by leucocytes will be studied by radiolabeling and immunoprecipitation methods. PEP binding to leucocytes and placental cell membranes will be examined by radioligand technique. Leucocytic proliferation response to PEP will be quantitated by 3H-thymidine incorporation. If the results of these studies fail to support the role of PEP in immunosuppression, efforts will be directed to examine the alternate possibilities that PEP is involved in steroid binding or in the control of placental proteases (which have been implicated in the placental cell invasion of maternal endometrial tissue). We hope the elucidation of hormonal control and role of this newly discovered major human pregnancy protein, namely PEP, will lead to the development of methods for the manipulation or control of human pregnancy.